Neurotransmitters were localized to specific populations of axonal endings and neurons in the medullary and spinal dorsal horns using the technique of immunocytochemistry at the light and EM level. Immunocytochemically labeled enkephalinergic (ENK) axonal endings were found to synapse directly on thalamic projection neurons labeled by retrograde transport of horseradish peroxidase. This observation demonstrates that one major site of opiate modulation of noxious input in the dorsal horn occurs directly on projection neurons, indicating that opiates act, at least in part, on post-synaptic receptors located on thalamic projection neurons. Several different morphological types of enkephalinergic neurons were observed in the dorsal horn. Based on the morphology of the dendrites of one type of neuron identified in the immunocytochemical studies, we propose that one class of ENK neurons in the dorsal horn are the lamina IIb islet cells. Serotonergic axonal endings were identified in the dorsal horn. The immunocytochemically labeled profiles are oriented primarily in the rostro-caudal plane and are found in all lamina. Ultrastructurally, most are dome shaped endings whih synapse on dendritic shafts and spines.